p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells

S. Wang, P. Bray, T. McCaffrey, K. March, B. L. Hempstead, R. Kraemer

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

The development of atherosclerotic lesions results from aberrant cell migration, proliferation, and extracellular matrix production. In advanced lesions, however, cellular apoptosis, leading to lesion remodeling, predominates. During lesion formation, the neurotrophins and the neurotrophin receptor tyrosine kinases, trks B and C, are induced and mediate smooth muscle cell migration. Here we demonstrate that a second neurotrophin receptor, p75(NTR), is expressed by established human atherosclerotic lesions and Late lesions that develop after balloon injury of the rat thoracic aorta. The p75(NTR), a member of the tumor necrosis factor/FAS receptor family, can modulate trk receptor function as well as initiate cell death when expressed in cells of the nervous system that lack kinase-active trk receptors, p75(NTR) expression colocalizes to neointimal cells, which express smooth muscle cell α-actin and are expressed by cultured human endarterectomy-derived cells (HEDC). Areas of the plaque expressing p75(NTR) demonstrate increased TUNEL positivity, and HEDC undergo apoptosis in response to the neurotrophins. Finally, neurotrophins also induced apoptosis of a smooth muscle cell line genetically manipulated to express p75(NTR), but lacking trk receptor expression. These studies identify the regulated expression of neurotrophins and p75(NTR) as an inducer of smooth muscle cell apoptosis in atherosclerotic lesions.

Original languageEnglish (US)
Pages (from-to)1247-1258
Number of pages12
JournalAmerican Journal of Pathology
Volume157
Issue number4
StatePublished - 2000
Externally publishedYes

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Nerve Growth Factor Receptor
Nerve Growth Factors
Vascular Smooth Muscle
Smooth Muscle Myocytes
Apoptosis
Endarterectomy
Cell Movement
Nerve Growth Factor Receptors
Tumor Necrosis Factor Receptors
In Situ Nick-End Labeling
Thoracic Aorta
Protein-Tyrosine Kinases
Nervous System
Extracellular Matrix
Actins
Cell Death
Phosphotransferases
Cell Proliferation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Wang, S., Bray, P., McCaffrey, T., March, K., Hempstead, B. L., & Kraemer, R. (2000). p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells. American Journal of Pathology, 157(4), 1247-1258.

p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells. / Wang, S.; Bray, P.; McCaffrey, T.; March, K.; Hempstead, B. L.; Kraemer, R.

In: American Journal of Pathology, Vol. 157, No. 4, 2000, p. 1247-1258.

Research output: Contribution to journalArticle

Wang, S, Bray, P, McCaffrey, T, March, K, Hempstead, BL & Kraemer, R 2000, 'p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells', American Journal of Pathology, vol. 157, no. 4, pp. 1247-1258.
Wang S, Bray P, McCaffrey T, March K, Hempstead BL, Kraemer R. p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells. American Journal of Pathology. 2000;157(4):1247-1258.
Wang, S. ; Bray, P. ; McCaffrey, T. ; March, K. ; Hempstead, B. L. ; Kraemer, R. / p75(NTR) mediates neurotrophin-induced apoptosis of vascular smooth muscle cells. In: American Journal of Pathology. 2000 ; Vol. 157, No. 4. pp. 1247-1258.
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